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Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of Europe

Meat and fish consumption and the risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition

Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 493,179 EPIC participants, recruited between 1992 an

Genomewide Association Study Using a High-Density Single Nucleotide Polymorphism Array and Case-Control Design Identifies a Novel Essential Hypertension Susceptibility Locus in the Promoter Region of Endothelial NO Synthase.

Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases

Emerging biomarkers and intervention targets for immune-modulation of atherosclerosis - A review of the experimental evidence.

The role of inflammation in atherosclerosis and plaque vulnerability is well recognized. However, it is only during recent years it has become evident that this inflammation is modulated by immune responses against plaque antigens such as oxidized LDL. Interestingly, both protective and pathogenic immune responses exist and experimental data from animal studies suggest that modulation of these imm

Inhibition of IAPP and IAPP((20-29)) Fibrillation by Polymeric Nanoparticles

The fibrillation process of the islet amyloid polypeptide (IAPP) and its fragment (IAPP((20-29))) was studied by means of Thioflavin T (ThT) fluorescence and transmission electron microscopy in the absence and presence of N-isopropylacrylamide:N-tert-butylacrylamide (NiPAM:BAM) copolymeric nanoparticles. The process was found to be strongly affected by the presence of the nanoparticles, which reta

Improving emergency response capability : an approach for strengthening learning from emergency response evaluations

The objectives of this study are to develop and demonstrate an approach to improve emergency response capability by strengthening individual and organisational learning from the evaluations of specific emergency responses. An approach was developed based on theories of individual and organisational learning. It was applied to evaluations of three instances of emergency response in the city of Malm

Comparability : Manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14-15 September 2015

This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this 'may be difficult for cell-based medicinal products'. T

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study

Background:Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods:Among 477 312 participants, intakes of

Echocardiographic consequences of smoking status in middle-aged subjects

Background: Smoking is known to have many short- and long-term cardiovascular effects. Cardiac index (CI), which is cardiac output indexed to body surface area, is considered to be a valid measure of cardiac performance. We investigated whether there were any differences in CI or other echocardiographic variables between never smokers, ex-smokers, and current smokers in a cardiopulmonary healthy p

Worldwide trends in diabetes since 1980 : A pooled analysis of 751 population-based studies with 4.4 million participants

Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with d

Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease

The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer's disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as

IL-8 predicts early mortality in patients with acute hypercapnic respiratory failure treated with noninvasive positive pressure ventilation

Background: Patients with Acute Hypercapnic Respiratory Failure (AHRF) who are unresponsive to appropriate medical treatment, are often treated with Noninvasive Positive Pressure Ventilation (NPPV). Clinical predictors of the outcome of this treatment are scarce. Therefore, we evaluated the role of the biomarkers IL-8 and GDF-15 in predicting 28-day mortality in patients with AHRF who receive trea

Pharmacokinetic Evaluation of Once-Weekly and Once-Monthly Buprenorphine Subcutaneous Injection Depots (CAM2038) Versus Intravenous and Sublingual Buprenorphine in Healthy Volunteers Under Naltrexone Blockade : An Open-Label Phase 1 Study

Introduction: CAM2038 q1w (once weekly) and q4w (once monthly) are investigational buprenorphine subcutaneous (SC) formulations based on FluidCrystal® injection depot technology. These two drug products are being developed for opioid dependence treatment, with a target for once-weekly and once-monthly SC dosing. The rationale for developing two products with different dosing frequencies is that tr

Dust-free bleaching powder may not prevent symptoms in hairdressers with bleaching-associated rhinitis

Objective: Hairdressers have an increased risk for airway symptoms especially when using hairbleaching powder containing persulfate. To minimize exposure, dust-free bleaching powder (DFP) has been made available. We studied the effects of regular powder (RP) or DFP on the airway symptoms of hairdressers with hair-bleaching associated rhinitis. Methods: Twelve hairdressers each performed three hair

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer : Extended Analysis of the Phase 3 PREVAIL Study

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final